Combination Chemotherapy, Rituximab, and Ixazomib Citrate in Treating Patients With Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the effects, good and bad of a new drug called ixazomib (also called MLN9708), when it is given along with a common treatment combination, called Dose-Adjusted EPOCH-R (DA-EPOCH-R, for short). This is a type of study called a phase I/II trial. In the phase I part, the dose of the study drug (ixazomib) will be adjusted (either up or down) to find the maximum (highest) dose that does not cause excessive (too many) harmful side effects. In the phase II part, this dose of ixazomib will be given at the maximum safe dose found in phase I. In both phase I and II, DA-EPOCH-R will be adjusted between cycles depending on how blood cell levels are affected between cycles. Ixazomib is considered investigational because it is not approved by the U.S. Food and Drug Administration (FDA). DA-EPOCH-R is a combination chemotherapy treatment developed over the last 14-15 years, and each of the drugs in this regimen is FDA-approved and considered part of the standard of care.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- To evaluate the safety of ixazomib (ixazomib citrate) given with dose-adjusted etoposide, prednisone, vincristine (vincristine sulfate), cyclophosphamide, doxorubicin (doxorubicin hydrochloride), and rituximab (DA-EPOCH-R) in patients with aggressive, v-myc avian myelocytomatosis viral oncogene homolog (MYC)-aberrant lymphoid malignancies, and to determine the recommended phase II dose (RP2D) of the combination. (Phase I) II. To evaluate the efficacy, as measured by 12-month progression free survival (PFS), of ixazomib given with DA-EPOCH-R in patients with aggressive, MYC-aberrant lymphoid malignancies. (Phase II)
SECONDARY OBJECTIVES:
-
Further evaluate the frequency and severity of toxicity. II. Further evaluate the clinical efficacy, as measured by response rate and overall survival (OS).
-
Assess the predictive value of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) scans on PFS.
TERTIARY OBJECTIVES:
-
Determine the impact of cell of origin (COO) upon response rate, PFS, and OS.
-
Assess the feasibility and outcomes of consolidation stem cell transplant (SCT).
OUTLINE: This is a phase I, dose-escalation study of ixazomib citrate followed by a phase II study.
INDUCTION:
Patients receive ixazomib citrate orally (PO) on day 1 and day 8 or 15; etoposide intravenously (IV), vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO twice daily (BID) on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5.
CENTRAL NERVOUS SYSTEM (CNS) PROPHYLAXIS:
Patients with a negative lumbar puncture (LP) receive methotrexate intrathecally (IT) once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly.
MAINTENANCE:
Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year (or as long as deriving benefit) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (combination chemotherapy, rituximab, ixazomib) INDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT or intraventricularly
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Drug: Ixazomib Citrate
Given PO
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Methotrexate
Given IT or intraventricularly
Other Names:
Drug: Prednisone
Given PO
Other Names:
Biological: Rituximab
Given IV
Other Names:
Drug: Therapeutic Hydrocortisone
Given IT or intraventricularly
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- To Determine the Recommended Phase II Dose (RP2D) of Ixazomib in Combination With DA-EPOCH-R. [The first 21 days of treatment]
The RP2D will be determined by the evaluation of dose-limiting toxicities (DLT) to find the Maximum Tolerated Dose (MTD) which will constitute the RP2D. DLTs will be defined as the occurrence of ≥ Grade 3 toxicity experienced during the first cycle (3 weeks or 21 days) of study treatment, will be determined, except for cytopenias. The dose of ixazomib will start at 2.3 mg weekly (for phase I patients) when given concurrently with DA-EPOCH-R. Single-subject cohorts (escalating in ixazomib dose) will be enrolled until the MTD is encountered, after which expansion to 3-subject cohorts will be undertaken. The MTD from phase I will equate the RP2D for ixazomib given in conjunction with DA-EPOCH-R.
- 12-month PFS (Progression Free Survival) of Treatment With Ixazomib in Combination With DA-EPOCH-R (Phase II) [Up to 12 months from initiation of treatment]
12-month PFS will be defined as the percentage of patients alive and progression free 12 months from start of therapy. Patients lost to follow up will be censored from last point of contact. PFS was calculated using a Kplan-meier estimation with the probability of patients being progression free at 12 months, presented as the percentage based on this probability.
Secondary Outcome Measures
- Toxicity of Treatment With Ixazomib in Combination With DA-EPOCH-R [Assessed at the beginning each cycle with up to 6 cycles of induction treatment and up to 13 cycles of maintenance treatment (1 cycle =21 days) and at approximately 21 days after the last treatment.]
Adverse events will be assessed using CTCAE v 4.03. In general grading will be as follows: Mild (grade 1): the event causes discomfort without disruption of normal daily activities. Moderate (grade 2): the event causes discomfort that affects normal daily activities. Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Life-threatening (grade 4): the patient was at risk of death at the time of the event. Fatal (grade 5): the event caused death.
- Overall Survival (OS) [Up to approximately 30 months]
OS will be defined as freedom from death by any cause and measured from time of treatment initiation and completion of follow up or death from any cause.
- Response Rate [After 2 cycles, then after 6 cycles and then at the discretion of the investigator for up to 13 maintenance cycles (1 cycle = 21 days)]
Anti-tumor activity will be defined as the detection of SD (Stable Disease), Partial Response (PR), or CR (Complete Remission) by CT or PET/CT scan, and/or resolution of marrow-only involvement. CR and PR will each be assessed according to the Revised Response Criteria for Malignant Lymphoma. Assessments will be performed after cycles 2 and 6, then at the discretion of the investigator. In general: CR-Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms PR-At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by ≥50% in their SPD or, for single nodules, in the greatest transverse diameter. No new sites of disease should be observed. SD-fails to attain the criteria needed for a CR or PR, but does not fulfill those for progressive disease
- Assess the Predictive Value of FDG-PET/CT Scans on PFS [Up to 1 year after treatment stopped]
Patients will be categorized as either FDG-PET (+) or (-) at interim and end-of treatment imaging.
Other Outcome Measures
- Determine the Impact of Cell of Origin (COO) Upon Response Rate, PFS, and OS [Up to 1 year]
Impact of COO defined as germinal center B-cell (GCB) and non-GCB via the Hans algorithm upon response rate, PFS, and OS (applicable only to patients with DLBCL).
- Consolidation SCT (Stem Cell Transplant) [Up to 1 year]
Feasibility and outcomes of consolidation SCT will be assessed. Patients will be grouped by whether consolidative SCT was performed in first remission, with PFS compared across groups (SCT vs. non-SCT).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have a histological diagnosis of any of the following (all stages allowed):
-
Diffuse large b-cell lymphoma (DLBCL) (including transformation from a previously indolent non-Hodgkin lymphoma [NHL], so long as no prior systemic treatment was given for the indolent NHL)
-
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma
-
Burkitt lymphoma
-
MYC+ plasmablastic lymphoma by histology
-
Patients must have measurable disease (defined as >= 1.5 cm in diameter)
-
Patients must have MYC-rearrangement, as determined by fluorescent in-situ hybridization (FISH) (does not require central review)
-
The following results must be available or pending at time of registration, though results will not affect enrollment/treatment:
-
B-cell chronic lymphocytic leukemia (CLL)/lymphoma (BCL)-2 rearrangement by FISH
-
BCL-6 rearrangement by FISH NOTE: although not required, it is encouraged that MYC and BCL-2 be measured by immunohistochemistry (IHC) and clearly documented
-
Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
-
Absolute neutrophil count (ANC) >= 1,000/mm^3
-
Platelets >= 75,000/mm^3
-
Total bilirubin =< 1.5 x upper limit of normal (ULN); NOTE: exceptions can be granted from principal investigator (PI) for instances of Gilbert's disease, and/or primarily indirect bilirubinemia, if due to recent transfusion and/or hemolysis
-
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SPGT]) =< 3 X institutional ULN
-
Calculated creatinine clearance >= 30 mL/min
-
NOTE: platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before registration; these requirements do not apply to those with marrow involvement of lymphoma (any extent)
-
Female patients must meet one of the following criteria:
-
Postmenopausal for at least 1 year prior to registration
-
Surgically sterile
-
Of childbearing potential and agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug
-
Of childbearing potential and agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject NOTE: periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
-
Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
-
Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug
-
Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject NOTE: periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
-
Females of child-bearing potential (FOCBP) must have a negative pregnancy test within
days prior to registration on study
- Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
Exclusion Criteria:
-
Patients who have had more than one cycle of prior chemoimmunotherapy for diagnosis of NHL are not eligible; NOTE: such patients must have fully recovered (ie, =< grade 1 toxicity) from the reversible effects of prior chemotherapy before starting treatment on the current protocol
-
Patients who have had major surgery within 4 weeks prior to registration are not eligible
-
Patients who have had radiotherapy within 14 days before registration are not eligible; NOTE: If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
-
Patients who have an infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment are not eligible
-
Patients who have evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months are not eligible
-
Patients who have undergone systemic treatment, within 14 days prior to registration, with strong inhibitors of cytochrome P450 superfamily (CYP)1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort are not eligible
-
Patients who have a clinically active hepatitis B or C virus infection are not eligible; NOTE: those with evidence of exposure to hepatitis B virus (HBV) may enroll so long as HBV viral load is negative AND subject is willing/able to take appropriate antiviral prophylaxis to prevent reactivation
-
Patients with any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol are not eligible
-
Patients who have a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent are not eligible
-
Patients who have a known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing are not eligible
-
Patients who have been diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease are not eligible; NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
-
Patients who have >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period are not eligible
-
Patients who are participating in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of registration and throughout the duration of this trial are not eligible
-
Female patients who are nursing or have a positive pregnancy test during screening are not eligible
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Northwestern University | Chicago | Illinois | United States | 60611 |
2 | Tufts University | Medford | Massachusetts | United States | 02155 |
3 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08901 |
4 | Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Cleveland | Ohio | United States | 44195 |
5 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Northwestern University
- National Cancer Institute (NCI)
- Millennium Pharmaceuticals, Inc.
Investigators
- Principal Investigator: Barbara Pro, MD, Northwestern University
Study Documents (Full-Text)
More Information
Publications
None provided.- NU 14H09
- NCI-2015-00400
- X16042
- STU00200596
- NU 14H09
- P30CA060553
Study Results
Participant Flow
Recruitment Details | The study opened to accrual on Aug 24, 2015 with the first patient being enrolled and starting treatment on 10.28.2015. The study closed to any further accrual on October 1sts 2019 with 38 patients enrolled on study. The study closed prior to reaching full accrual goal of up to 55 patients. |
---|---|
Pre-assignment Detail | First patient was enrolled to Cohort 1. Second patient enrolled to Cohort 2. Third patient enrolled to Cohort 3. Forth and fifth patient enrolled to Cohort 2. All further patients enrolled to phase II (same dose as Cohort 2). |
Arm/Group Title | Treatment- Cohort 1(Combination Chemotherapy, Rituximab, Ixazomib 2.3 mg) | Treatment Cohort 2 and Phase II (Combination Chemotherapy, Rituximab, Ixazomib 3 mg) | Treatment - Cohort 3 (Combination Chemotherapy, Rituximab, Ixazomib 4 mg) |
---|---|---|---|
Arm/Group Description | INDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Cytarabine: Given IT or intraventricularly Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ixazomib Citrate: Given PO Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IT or intraventricularly Prednisone: Given PO Rituximab: Given IV Therapeutic Hydrocortisone: Given IT or intraventricularly Vincristine Sulfate: Given IV | NDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Cytarabine: Given IT or intraventricularly Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ixazomib Citrate: Given PO Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IT or intraventricularly Prednisone: Given PO Rituximab: Given IV Therapeutic Hydrocortisone: Given IT or intraventricularly Vincristine Sulfate: Given IV | NDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Cytarabine: Given IT or intraventricularly Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ixazomib Citrate: Given PO Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IT or intraventricularly Prednisone: Given PO Rituximab: Given IV Therapeutic Hydrocortisone: Given IT or intraventricularly Vincristine Sulfate: Given IV |
Period Title: Induction Treatment (6 Cycles) | |||
STARTED | 1 | 36 | 1 |
Reached First Evaluable Response | 1 | 34 | 1 |
Complete 6 Cycles | 1 | 30 | 1 |
COMPLETED | 1 | 30 | 1 |
NOT COMPLETED | 0 | 6 | 0 |
Period Title: Induction Treatment (6 Cycles) | |||
STARTED | 1 | 21 | 1 |
Started Maintenance Treatment | 1 | 21 | 1 |
COMPLETED | 1 | 21 | 1 |
NOT COMPLETED | 0 | 0 | 0 |
Period Title: Induction Treatment (6 Cycles) | |||
STARTED | 1 | 32 | 1 |
COMPLETED | 1 | 29 | 1 |
NOT COMPLETED | 0 | 3 | 0 |
Baseline Characteristics
Arm/Group Title | Treatment- Cohort 1(Combination Chemotherapy, Rituximab, Ixazomib 2.3 mg) | Treatment Cohort 2 and Phase II (Combination Chemotherapy, Rituximab, Ixazomib 3 mg) | Treatment - Cohort 3 (Combination Chemotherapy, Rituximab, Ixazomib 4 mg) | Total |
---|---|---|---|---|
Arm/Group Description | INDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Cytarabine: Given IT or intraventricularly Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ixazomib Citrate: Given PO Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IT or intraventricularly Prednisone: Given PO Rituximab: Given IV Therapeutic Hydrocortisone: Given IT or intraventricularly Vincristine Sulfate: Given IV | NDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Cytarabine: Given IT or intraventricularly Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ixazomib Citrate: Given PO Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IT or intraventricularly Prednisone: Given PO Rituximab: Given IV Therapeutic Hydrocortisone: Given IT or intraventricularly Vincristine Sulfate: Given IV | NDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Cytarabine: Given IT or intraventricularly Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ixazomib Citrate: Given PO Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IT or intraventricularly Prednisone: Given PO Rituximab: Given IV Therapeutic Hydrocortisone: Given IT or intraventricularly Vincristine Sulfate: Given IV | Total of all reporting groups |
Overall Participants | 1 | 36 | 1 | 38 |
Age (Count of Participants) | ||||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
0
0%
|
25
69.4%
|
0
0%
|
25
65.8%
|
>=65 years |
1
100%
|
11
30.6%
|
1
100%
|
13
34.2%
|
Sex: Female, Male (Count of Participants) | ||||
Female |
0
0%
|
11
30.6%
|
0
0%
|
11
28.9%
|
Male |
1
100%
|
25
69.4%
|
1
100%
|
27
71.1%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
0
0%
|
1
2.8%
|
0
0%
|
1
2.6%
|
Not Hispanic or Latino |
1
100%
|
35
97.2%
|
1
100%
|
37
97.4%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | ||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
3
8.3%
|
0
0%
|
3
7.9%
|
White |
1
100%
|
33
91.7%
|
1
100%
|
35
92.1%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
Title | To Determine the Recommended Phase II Dose (RP2D) of Ixazomib in Combination With DA-EPOCH-R. |
---|---|
Description | The RP2D will be determined by the evaluation of dose-limiting toxicities (DLT) to find the Maximum Tolerated Dose (MTD) which will constitute the RP2D. DLTs will be defined as the occurrence of ≥ Grade 3 toxicity experienced during the first cycle (3 weeks or 21 days) of study treatment, will be determined, except for cytopenias. The dose of ixazomib will start at 2.3 mg weekly (for phase I patients) when given concurrently with DA-EPOCH-R. Single-subject cohorts (escalating in ixazomib dose) will be enrolled until the MTD is encountered, after which expansion to 3-subject cohorts will be undertaken. The MTD from phase I will equate the RP2D for ixazomib given in conjunction with DA-EPOCH-R. |
Time Frame | The first 21 days of treatment |
Outcome Measure Data
Analysis Population Description |
---|
1 patient enrolled at 2.3 mg of ixazomib, 3 patients enrolled at 3 mg of ixazomib, 1 patient enrolled at 4 mg ixazomib in phase I were evaluable for this endpoint. |
Arm/Group Title | Treatment (Combination Chemotherapy, Rituximab, Ixazomib) |
---|---|
Arm/Group Description | INDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Cytarabine: Given IT or intraventricularly Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ixazomib Citrate: Given PO Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IT or intraventricularly Prednisone: Given PO Rituximab: Given IV Therapeutic Hydrocortisone: Given IT or intraventricularly Vincristine Sulfate: Given IV |
Measure Participants | 5 |
Number [mg] |
3
|
Title | 12-month PFS (Progression Free Survival) of Treatment With Ixazomib in Combination With DA-EPOCH-R (Phase II) |
---|---|
Description | 12-month PFS will be defined as the percentage of patients alive and progression free 12 months from start of therapy. Patients lost to follow up will be censored from last point of contact. PFS was calculated using a Kplan-meier estimation with the probability of patients being progression free at 12 months, presented as the percentage based on this probability. |
Time Frame | Up to 12 months from initiation of treatment |
Outcome Measure Data
Analysis Population Description |
---|
Only patients included in the phase II dose are included in this endpoint per protocol. |
Arm/Group Title | Treatment (Combination Chemotherapy, Rituximab, Ixazomib) |
---|---|
Arm/Group Description | INDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Cytarabine: Given IT or intraventricularly Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ixazomib Citrate: Given PO Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IT or intraventricularly Prednisone: Given PO Rituximab: Given IV Therapeutic Hydrocortisone: Given IT or intraventricularly Vincristine Sulfate: Given IV |
Measure Participants | 36 |
Number (95% Confidence Interval) [probability (%) of patients alive] |
75.84
|
Title | Toxicity of Treatment With Ixazomib in Combination With DA-EPOCH-R |
---|---|
Description | Adverse events will be assessed using CTCAE v 4.03. In general grading will be as follows: Mild (grade 1): the event causes discomfort without disruption of normal daily activities. Moderate (grade 2): the event causes discomfort that affects normal daily activities. Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Life-threatening (grade 4): the patient was at risk of death at the time of the event. Fatal (grade 5): the event caused death. |
Time Frame | Assessed at the beginning each cycle with up to 6 cycles of induction treatment and up to 13 cycles of maintenance treatment (1 cycle =21 days) and at approximately 21 days after the last treatment. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Overall Survival (OS) |
---|---|
Description | OS will be defined as freedom from death by any cause and measured from time of treatment initiation and completion of follow up or death from any cause. |
Time Frame | Up to approximately 30 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Response Rate |
---|---|
Description | Anti-tumor activity will be defined as the detection of SD (Stable Disease), Partial Response (PR), or CR (Complete Remission) by CT or PET/CT scan, and/or resolution of marrow-only involvement. CR and PR will each be assessed according to the Revised Response Criteria for Malignant Lymphoma. Assessments will be performed after cycles 2 and 6, then at the discretion of the investigator. In general: CR-Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms PR-At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by ≥50% in their SPD or, for single nodules, in the greatest transverse diameter. No new sites of disease should be observed. SD-fails to attain the criteria needed for a CR or PR, but does not fulfill those for progressive disease |
Time Frame | After 2 cycles, then after 6 cycles and then at the discretion of the investigator for up to 13 maintenance cycles (1 cycle = 21 days) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Assess the Predictive Value of FDG-PET/CT Scans on PFS |
---|---|
Description | Patients will be categorized as either FDG-PET (+) or (-) at interim and end-of treatment imaging. |
Time Frame | Up to 1 year after treatment stopped |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Determine the Impact of Cell of Origin (COO) Upon Response Rate, PFS, and OS |
---|---|
Description | Impact of COO defined as germinal center B-cell (GCB) and non-GCB via the Hans algorithm upon response rate, PFS, and OS (applicable only to patients with DLBCL). |
Time Frame | Up to 1 year |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Consolidation SCT (Stem Cell Transplant) |
---|---|
Description | Feasibility and outcomes of consolidation SCT will be assessed. Patients will be grouped by whether consolidative SCT was performed in first remission, with PFS compared across groups (SCT vs. non-SCT). |
Time Frame | Up to 1 year |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | Adverse events were collected at the beginning of each cycle for up to 6 induction cycles and up to 13 maintenance cycles (1 cycle = 21 days) and 21 days after the last study treatment | |
---|---|---|
Adverse Event Reporting Description | Secondary endpoints are written to have phase I & II patient data combined in analysis. Due to the way that adverse event data collected was analysed (i.e. phase I/II data was analysed combined regardless of dose) all patients data here is shown as one cohort regardless of initial dose of ixazomib given. This is due to the way the protocol was written and that only 2 patients out of 38 received a different initial starting dose (and the starting dose for all in maintenance was 4 mg). | |
Arm/Group Title | Treatment (Combination Chemotherapy, Rituximab, Ixazomib) | |
Arm/Group Description | INDUCTION: Patients receive ixazomib citrate PO on day 1 and day 8 or 15; etoposide IV, vincristine sulfate IV, and doxorubicin hydrochloride IV continuously over 96 hours on days 1-4; prednisone PO BID on days 1-5; rituximab IV should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr on day 1; and cyclophosphamide IV over 90 minutes on day 5. CNS PROPHYLAXIS: Patients with a negative LP receive methotrexate IT once per course. Patients with a positive LP receive methotrexate IT or intraventricularly OR cytarabine IT or intraventricularly OR methotrexate IT or intraventricularly, cytarabine IT or intraventricularly, and therapeutic hydrocortisone IT or intraventricularly. MAINTENANCE: Patients not treated with consolidative SCT, receive ixazomib citrate PO BID on days 1, 8, and 15. Treatment repeats every 28 days for up to one year in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Cytarabine: Given IT or intraventricularly Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ixazomib Citrate: Given PO Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IT or intraventricularly Prednisone: Given PO Rituximab: Given IV Therapeutic Hydrocortisone: Given IT or intraventricularly Vincristine Sulfate: Given IV | |
All Cause Mortality |
||
Treatment (Combination Chemotherapy, Rituximab, Ixazomib) | ||
Affected / at Risk (%) | # Events | |
Total | 6/38 (15.8%) | |
Serious Adverse Events |
||
Treatment (Combination Chemotherapy, Rituximab, Ixazomib) | ||
Affected / at Risk (%) | # Events | |
Total | 20/38 (52.6%) | |
Blood and lymphatic system disorders | ||
Febrile Neutropenia | 7/38 (18.4%) | 8 |
Febrile neutropenia | 1/38 (2.6%) | 1 |
Cardiac disorders | ||
Cardiac Arrest | 1/38 (2.6%) | 1 |
Gastrointestinal disorders | ||
Esophageal perforation | 1/38 (2.6%) | 1 |
Small intestine and colonic perforation | 1/38 (2.6%) | 1 |
Infections and infestations | ||
Cholecystitis | 1/38 (2.6%) | 1 |
Lung infection | 1/38 (2.6%) | 1 |
duodenitis | 1/38 (2.6%) | 1 |
Sepsis | 1/38 (2.6%) | 1 |
parainfluenza 3 | 1/38 (2.6%) | 1 |
Urinary tract infection | 1/38 (2.6%) | 1 |
Lung infection | 1/38 (2.6%) | 1 |
Sepsis | 1/38 (2.6%) | 1 |
Injury, poisoning and procedural complications | ||
Spinal fracture (lumbar) | 1/38 (2.6%) | 1 |
Metabolism and nutrition disorders | ||
Hyponatremia | 1/38 (2.6%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
gastric adenocarcinoma | 1/38 (2.6%) | 1 |
Renal and urinary disorders | ||
Acute kidney injury | 1/38 (2.6%) | 1 |
Acute kidney injury | 1/38 (2.6%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
COPD Exacerbation | 1/38 (2.6%) | 1 |
Respiratory failure | 1/38 (2.6%) | 1 |
Respiratory failure | 1/38 (2.6%) | 1 |
Vascular disorders | ||
Thromboembolic event | 1/38 (2.6%) | 1 |
Thromboembolic event - pulmonary embolism | 1/38 (2.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Treatment (Combination Chemotherapy, Rituximab, Ixazomib) | ||
Affected / at Risk (%) | # Events | |
Total | 38/38 (100%) | |
Blood and lymphatic system disorders | ||
Anemia | 38/38 (100%) | |
Blood and lymphatic system disorders - Other, specify | 3/38 (7.9%) | |
Febrile neutropenia | 3/38 (7.9%) | |
Lymph node pain | 3/38 (7.9%) | |
Leukocytosis | 2/38 (5.3%) | |
Cardiac disorders | ||
Sinus tachycardia | 12/38 (31.6%) | |
Cardiac disorders - Other, specify | 9/38 (23.7%) | |
Palpitations | 2/38 (5.3%) | |
Atrial fibrillation | 1/38 (2.6%) | |
Chest pain - cardiac | 1/38 (2.6%) | |
Left ventricular systolic dysfunction | 1/38 (2.6%) | |
Sinus bradycardia | 1/38 (2.6%) | |
Ear and labyrinth disorders | ||
Tinnitus | 4/38 (10.5%) | |
Ear and labyrinth disorders - Other, specify | 3/38 (7.9%) | |
Ear pain | 1/38 (2.6%) | |
Endocrine disorders | ||
Hypothyroidism | 3/38 (7.9%) | |
Endocrine disorders - Other, specify | 1/38 (2.6%) | |
Eye disorders | ||
Blurred vision | 5/38 (13.2%) | |
Eye disorders - Other, specify | 5/38 (13.2%) | |
Cataract | 3/38 (7.9%) | |
Retinal detachment | 2/38 (5.3%) | |
Watering eyes | 2/38 (5.3%) | |
Eye pain | 1/38 (2.6%) | |
Vitreous hemorrhage | 1/38 (2.6%) | |
Gastrointestinal disorders | ||
Constipation | 32/38 (84.2%) | |
Nausea | 29/38 (76.3%) | |
Mucositis oral | 22/38 (57.9%) | |
Diarrhea | 19/38 (50%) | |
Vomiting | 16/38 (42.1%) | |
Abdominal pain | 14/38 (36.8%) | |
Gastrointestinal disorders - Other, specify | 8/38 (21.1%) | |
Hemorrhoids | 7/38 (18.4%) | |
Dry mouth | 6/38 (15.8%) | |
Abdominal distension | 5/38 (13.2%) | |
Dyspepsia | 4/38 (10.5%) | |
Dysphagia | 4/38 (10.5%) | |
Gastroesophageal reflux disease | 4/38 (10.5%) | |
Bloating | 3/38 (7.9%) | |
Flatulence | 3/38 (7.9%) | |
Oral pain | 3/38 (7.9%) | |
Toothache | 2/38 (5.3%) | |
Anal hemorrhage | 1/38 (2.6%) | |
Fecal incontinence | 1/38 (2.6%) | |
Lower gastrointestinal hemorrhage | 1/38 (2.6%) | |
Upper gastrointestinal hemorrhage | 1/38 (2.6%) | |
General disorders | ||
Fatigue | 35/38 (92.1%) | |
Edema limbs | 20/38 (52.6%) | |
Pain | 15/38 (39.5%) | |
Chills | 10/38 (26.3%) | |
Fever | 9/38 (23.7%) | |
General disorders and administration site conditions - Other, specify | 9/38 (23.7%) | |
Localized edema | 8/38 (21.1%) | |
Infusion related reaction | 5/38 (13.2%) | |
Non-cardiac chest pain | 4/38 (10.5%) | |
Flu like symptoms | 2/38 (5.3%) | |
Gait disturbance | 2/38 (5.3%) | |
Malaise | 2/38 (5.3%) | |
Edema face | 1/38 (2.6%) | |
Facial pain | 1/38 (2.6%) | |
Infusion site extravasation | 1/38 (2.6%) | |
Hepatobiliary disorders | ||
Cholecystitis | 1/38 (2.6%) | |
Hepatobiliary disorders - Other, specify | 1/38 (2.6%) | |
Immune system disorders | ||
Immune system disorders - Other, specify | 2/38 (5.3%) | |
Infections and infestations | ||
Infections and infestations - Other, specify | 7/38 (18.4%) | |
Urinary tract infection | 4/38 (10.5%) | |
Sepsis | 3/38 (7.9%) | |
Upper respiratory infection | 3/38 (7.9%) | |
Lung infection | 2/38 (5.3%) | |
Sinusitis | 2/38 (5.3%) | |
Enterocolitis infectious | 1/38 (2.6%) | |
Esophageal infection | 1/38 (2.6%) | |
Skin infection | 1/38 (2.6%) | |
Wound infection | 1/38 (2.6%) | |
Injury, poisoning and procedural complications | ||
Bruising | 7/38 (18.4%) | |
Fall | 1/38 (2.6%) | |
Injury, poisoning and procedural complications - Other, specify | 1/38 (2.6%) | |
Vascular access complication | 1/38 (2.6%) | |
Investigations | ||
Lymphocyte count decreased | 38/38 (100%) | |
Platelet count decreased | 38/38 (100%) | |
White blood cell decreased | 34/38 (89.5%) | |
Neutrophil count decreased | 33/38 (86.8%) | |
Alkaline phosphatase increased | 24/38 (63.2%) | |
Alanine aminotransferase increased | 22/38 (57.9%) | |
Weight loss | 22/38 (57.9%) | |
Aspartate aminotransferase increased | 21/38 (55.3%) | |
Investigations - Other, specify | 13/38 (34.2%) | |
Creatinine increased | 12/38 (31.6%) | |
Blood bilirubin increased | 8/38 (21.1%) | |
Weight gain | 4/38 (10.5%) | |
INR increased | 3/38 (7.9%) | |
Cholesterol high | 2/38 (5.3%) | |
Lymphocyte count increased | 1/38 (2.6%) | |
Urine output decreased | 1/38 (2.6%) | |
Metabolism and nutrition disorders | ||
Hypoalbuminemia | 37/38 (97.4%) | |
Hypocalcemia | 34/38 (89.5%) | |
Hypokalemia | 33/38 (86.8%) | |
Hyperglycemia | 24/38 (63.2%) | |
Hypophosphatemia | 24/38 (63.2%) | |
Hyponatremia | 20/38 (52.6%) | |
Anorexia | 13/38 (34.2%) | |
Hypernatremia | 10/38 (26.3%) | |
Hypomagnesemia | 10/38 (26.3%) | |
Hyperkalemia | 8/38 (21.1%) | |
Hypoglycemia | 7/38 (18.4%) | |
Metabolism and nutrition disorders - Other, specify | 7/38 (18.4%) | |
Hypercalcemia | 6/38 (15.8%) | |
Hyperuricemia | 6/38 (15.8%) | |
Dehydration | 4/38 (10.5%) | |
Obesity | 4/38 (10.5%) | |
Hypermagnesemia | 2/38 (5.3%) | |
Acidosis | 1/38 (2.6%) | |
Alkalosis | 1/38 (2.6%) | |
Tumor lysis syndrome | 1/38 (2.6%) | |
Musculoskeletal and connective tissue disorders | ||
Back pain | 16/38 (42.1%) | |
Bone pain | 10/38 (26.3%) | |
Generalized muscle weakness | 10/38 (26.3%) | |
Pain in extremity | 9/38 (23.7%) | |
Musculoskeletal and connective tissue disorder - Other, specify | 7/38 (18.4%) | |
Myalgia | 6/38 (15.8%) | |
Neck pain | 4/38 (10.5%) | |
Muscle weakness lower limb | 3/38 (7.9%) | |
Arthralgia | 2/38 (5.3%) | |
Chest wall pain | 2/38 (5.3%) | |
Arthritis | 1/38 (2.6%) | |
Musculoskeletal deformity | 1/38 (2.6%) | |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 2/38 (5.3%) | |
Nervous system disorders | ||
Peripheral sensory neuropathy | 30/38 (78.9%) | |
Headache | 20/38 (52.6%) | |
Dysgeusia | 15/38 (39.5%) | |
Dizziness | 14/38 (36.8%) | |
Paresthesia | 8/38 (21.1%) | |
Peripheral motor neuropathy | 4/38 (10.5%) | |
Tremor | 4/38 (10.5%) | |
Lethargy | 3/38 (7.9%) | |
Aphonia | 1/38 (2.6%) | |
Cerebrospinal fluid leakage | 1/38 (2.6%) | |
Dysesthesia | 1/38 (2.6%) | |
Dysphasia | 1/38 (2.6%) | |
Encephalopathy | 1/38 (2.6%) | |
Hypersomnia | 1/38 (2.6%) | |
Memory impairment | 1/38 (2.6%) | |
Nervous system disorders - Other, specify | 1/38 (2.6%) | |
Presyncope | 1/38 (2.6%) | |
Sinus pain | 1/38 (2.6%) | |
Vasovagal reaction | 1/38 (2.6%) | |
Pregnancy, puerperium and perinatal conditions | ||
Pregnancy, puerperium and perinatal conditions - Other, specify | 1/38 (2.6%) | |
Psychiatric disorders | ||
Anxiety | 16/38 (42.1%) | |
Insomnia | 14/38 (36.8%) | |
Depression | 12/38 (31.6%) | |
Confusion | 2/38 (5.3%) | |
Psychiatric disorders - Other, specify | 2/38 (5.3%) | |
Delirium | 1/38 (2.6%) | |
Renal and urinary disorders | ||
Renal and urinary disorders - Other, specify | 9/38 (23.7%) | |
Urinary frequency | 8/38 (21.1%) | |
Urinary incontinence | 3/38 (7.9%) | |
Acute kidney injury | 2/38 (5.3%) | |
Hematuria | 2/38 (5.3%) | |
Urinary retention | 2/38 (5.3%) | |
Reproductive system and breast disorders | ||
Reproductive system and breast disorders - Other, specify | 4/38 (10.5%) | |
Breast pain | 1/38 (2.6%) | |
Erectile dysfunction | 1/38 (2.6%) | |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 20/38 (52.6%) | |
Dyspnea | 18/38 (47.4%) | |
Nasal congestion | 15/38 (39.5%) | |
Respiratory, thoracic and mediastinal disorders - Other, specify | 14/38 (36.8%) | |
Sore throat | 9/38 (23.7%) | |
Postnasal drip | 5/38 (13.2%) | |
Sleep apnea | 5/38 (13.2%) | |
Epistaxis | 4/38 (10.5%) | |
Hoarseness | 4/38 (10.5%) | |
Productive cough | 4/38 (10.5%) | |
Allergic rhinitis | 3/38 (7.9%) | |
Atelectasis | 3/38 (7.9%) | |
Pleural effusion | 3/38 (7.9%) | |
Respiratory failure | 2/38 (5.3%) | |
Hiccups | 1/38 (2.6%) | |
Hypoxia | 1/38 (2.6%) | |
Pulmonary edema | 1/38 (2.6%) | |
Pulmonary hypertension | 1/38 (2.6%) | |
Sneezing | 1/38 (2.6%) | |
Wheezing | 1/38 (2.6%) | |
Skin and subcutaneous tissue disorders | ||
Skin and subcutaneous tissue disorders - Other, specify | 11/38 (28.9%) | |
Alopecia | 7/38 (18.4%) | |
Dry skin | 5/38 (13.2%) | |
Rash maculo-papular | 5/38 (13.2%) | |
Hyperhidrosis | 3/38 (7.9%) | |
Nail loss | 3/38 (7.9%) | |
Pruritus | 3/38 (7.9%) | |
Skin ulceration | 3/38 (7.9%) | |
Bullous dermatitis | 2/38 (5.3%) | |
Pain of skin | 2/38 (5.3%) | |
Rash acneiform | 2/38 (5.3%) | |
Erythema multiforme | 1/38 (2.6%) | |
Nail discoloration | 1/38 (2.6%) | |
Vascular disorders | ||
Hypertension | 34/38 (89.5%) | |
Thromboembolic event | 5/38 (13.2%) | |
Hypotension | 4/38 (10.5%) | |
Hot flashes | 3/38 (7.9%) | |
Hematoma | 1/38 (2.6%) | |
Lymphedema | 1/38 (2.6%) | |
Vascular disorders - Other, specify | 1/38 (2.6%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Barbara Pro, MD |
---|---|
Organization | Northwestern University |
Phone | 312-695-6832 |
barbara.pro@northwestern.edu |
- NU 14H09
- NCI-2015-00400
- X16042
- STU00200596
- NU 14H09
- P30CA060553